BackgroundThe purpose of this study was to investigate whether white matter microstructure is altered in patients suffering from systemic lupus erythematosus (SLE), and if so, whether such alterations differed between patients with and without neuropsychiatric symptoms.MethodsStructural MRI and diffusion tensor imaging (DTI) were performed in 64 female SLE patients (mean age 36.9 years, range 18.2–52.2 years) and 21 healthy controls (mean age 36.7 years, range 23.3–51.2 years) in conjunction with clinical examination, laboratory tests, cognitive evaluation, and self-assessment questionnaires. The patients were subgrouped according to the American College of Rheumatology Neuropsychiatric Systemic Lupus Erythematosus case definitions into non-neuropsychiatric SLE (nonNPSLE) and neuropsychiatric SLE (NPSLE).ResultsComparisons between the SLE group and healthy controls showed that the mean fractional anisotropy (FA) was significantly reduced in the right rostral cingulum (p = 0.038), the mid-sagittal corpus callosum (CC) (p = 0.050), and the forceps minor of the CC (p = 0.015). The mean diffusivity (MD) was significantly increased in the left hippocampal cingulum (p = 0.017). No significant differences in MD or FA values were identified between NPSLE and nonNPSLE patients. Disease duration among all SLE patients correlated significantly with reduced FA in the CC (p < 0.05). No correlations were found between DTI parameters and white matter hyperintensities, SLE Disease Activity Index-2000, Systemic Lupus International Collaborating Clinical/ACR Organ Damage Index, or Montgomery Asberg Depression Rate Score Self-report.ConclusionsWe found alterations of white matter microstructure in SLE patients that were related to disease duration and fatigue. Our results indicate that cerebral involvement in SLE is not isolated to the NPSLE subgroup.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1516-0) contains supplementary material, which is available to authorized users.

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

To investigate core resting state networks in SLE patients with and without neuropsychiatric symptoms by examining functional connectivity changes correlating with results of cognitive testing. Structural MRI and resting state‐fMRI (rs‐fMRI) were performed in 61 female SLE patients (mean age: 36.8 years, range 18.2–52.0 years) and 20 healthy controls (HC) (mean age 36.2 years, range 23.3–52.2 years) in conjunction with clinical examination and cognitive testing. Alterations in core resting state networks, not found in our healthy controls sample, correlated with cognitive performance gauged by neuropsychological tests in non‐neuropsychiatric SLE (nNP) as well as in neuropsychiatric SLE patients (NP). The observed pattern of increased functional connectivity in core resting state networks correlated with reduced cognitive performance on all cognitive domains tested and with a heavy focus on DM, CE, and DM–CE in the NP subgroup. Furthermore, we found that the observed alterations in memory and psychomotor speed correlated with disease duration. In SLE patients both with and without clinically overt neuropsychiatric manifestations, we found changes in the functional connectivity of core resting state networks essential to cognitive functions. These findings may represent a rewiring of functional architecture in response to neuronal damage and could indicate suboptimal compensatory mechanisms at play.